Increasing patient access to faecal microbiota transplantation with remote delivery: a cost analysis of outpatient versus home-based treatment

BackgroundThe 2017 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) Clostridium (Clostridioides) difficile infection (CDI) guideline update recommended treatment with fidaxomicin or vancomycin for CDI. We aimed to examine outpatient CDI treatment utilization before and after the guideline update and compare clinical outcomes associated with fidaxomicin versus vancomycin use.MethodsA pre-post study design was employed using Medicare data. CDI treatment utilization and clinical outcomes (4- and 8-week sustained response, CDI recurrence) were compared between patients indexed from April–September 2017 (preguideline period) and those indexed from April–September 2018 (postguideline period). Clinical outcomes associated with fidaxomicin versus vancomycin were compared using propensity score–matched analyses.ResultsFrom the pre- to postguideline period, metronidazole use decreased (initial CDI: 81.2% to 53.5%; recurrent CDI: 49.7% to 27.6%) while vancomycin (initial CDI: 17.9% to 44.9%; recurrent CDI: 48.1% to 66.4%) and fidaxomicin (initial CDI: 0.87% to 1.63%; recurrent CDI: 2.2% to 6.0%) use increased significantly (P < .001 for all). However, clinical outcomes did not improve. In propensity score–matched analyses, fidaxomicin versus vancomycin users had 4-week sustained response rates that were higher by 13.5% (95% confidence interval [CI], 4.0%–22.9%; P = .0058) and 30.0% (95% CI, 16.8%–44.3%; P = .0002) in initial and recurrent CDI cohorts, respectively. Recurrence rates were numerically lower for fidaxomicin in both cohorts.ConclusionsVancomycin use increased and metronidazole use decreased after the 2017 guideline update. Fidaxomicin use increased but remained low. Improved outcomes associated with fidaxomicin relative to vancomycin suggest benefits from its greater use in Medicare patients.

7542 Background: Hyperacute graft versus host disease (GVHD) after allogenic stem cell transplantation (SCT) has adverse outcomes with increased rates of chronic GVHD and relapse. GVHD risks include mismatched related or matched unrelated donors, myeloablative conditioning, heavy pretreatment, and donor-recipient sex mismatch. Clostridium difficile infection (CDI) is a leading cause of diarrhea in immunocompromised patients. Proposed microbiome effect on immunity and GVHD in allogenic SCT recipients prompts concern of microbiome modulation from CDI and antibiotics inciting GVDH. Methods: National Inpatient Sample database 2014 for hospitalizations with allogeneic SCT in patients ≥18yo. Characteristics (age, sex, race, insurance, graft source, hospital type, region, comorbidities) were compared for hospitalizations with and without CDI. Primary outcome was the difference in the incidence of GVHD during the transplant hospitalization between the 2 groups. Other outcomes were mortality, length of stay and hospital charges. Chi-square, t-test, and multivariate logistic regression utilized. Results: Of 6210 patients with allogenic SCT, 745 (12%) had CDI during the transplant hospitalization. In transplanted patients without CDI the average age was 55yo, 43.9% female, 69.5% Caucasian (C), 7.1% African American (AA), 8.6% Hispanic (H), 32.1% had Medicare/Medicaid, 61.8% private insurance, 5.7% uninsured, 44.7% had hypertension, 13.7% had diabetes, graft source was 84.3% PBSC (peripheral blood stem cells), 11.3% bone marrow, and 4.4% cord blood. CDI group the average age was 52.5yo, 45.3% female, 73% C, 4.7% AA, 8.1% H, 25.7% had Medicare/Medicaid, 66.2% private insurance, 8.1% uninsured, 41.9% had hypertension, 10.1% had diabetes, graft source was 83.8% PBSC, 10.8% bone marrow, and 5.4% cord blood. 25.7% of patients with CDI developed GVHD during that hospitalization while 14.2% of patients without CDI developed GVHD during the hospital stay (OR 2.1, p &lt; 0.001 multivariate analysis). GVHD during the hospitalization had no difference in length of stay (p = 0.32), total cost of stay (p = 0.50) or same hospitalization mortality (p = 0.94). Conclusions: Allogeneic SCT patients with CDI develop GVHD on the same hospitalization at significantly higher rates than patients without CDI. This is true after controlling for age, sex, race, insurance, comorbidities, graft source, hospital location, and type of institution. Despite known associations of early evidence of GVHD on relapse, overall mortality was not different between the two groups.

Compared with younger populations, adults 65 years and older are more likely to suffer infection-related morbidity and mortality, experience antibiotic-related adverse events, and acquire multidrug-resistant organisms. We developed a series of case-based discussions that stressed antibiotic stewardship while addressing management of common infections in older adults. Five 1-hour case-based discussions address recognition, diagnosis, and management of infections common in older adults, including those living in long-term care settings: urinary tract infections, upper respiratory tract infections, lower respiratory tract infections, skin and soft tissue infections, and Clostridium difficile infection. The education was implemented at the skilled nursing centers at 15 Veterans Affairs medical centers. Participants from an array of disciplines completed an educational evaluation for each session as well as a pre- and postcourse knowledge assessment. The number of respondents to the educational evaluation administered following each session ranged from 68 to 108. Learners agreed that each session met its learning objectives (4.80-4.89 on a 5-point Likert scale, 5 = strongly agree) and that they were likely to make changes (2.50-2.89 on a 3-point scale, 3 = highly likely to make changes). The average score on the five-question knowledge assessment increased from 3.6 (72%) to 3.9 (78%, p = .06). By stressing recognition of atypical signs and symptoms of infection in older adults, diagnostic tests, and antibiotic stewardship, this series of five case-based discussions enhanced clinical training of learners from several disciplines.

Introduction:Clostridium difficile infection (CDI) is associated with poor outcomes in hospitalized adults. Acute pancreatitis (AP) patients are commonly hospitalized and may be exposed to antibiotics predisposing to CDI. We examined the prevalence and health-care outcomes of CDI in patients with AP. Methods: We performed a cross-sectional analysis using 2012 Nationwide Inpatient Sample data. International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes were used to identify patients with AP (ICD-9:570.0) and CDI (ICD-9:008.45). Primary outcome variables included inpatient mortality, length of stay and total charges in patients with acute pancreatitis with or without CDI. Secondary outcomes included acute renal failure, acute respiratory failure and mechanical ventilation. Univariate and multivariable logistic regression (for categorical variables) and linear regression (for continuous variables) were performed. Multiple variable regression analysis controlled for differences in sex, age, race, location of hospital, patient residence, insurance, hospital size, region, co morbidities, weekend admission, type of admission, and type of hospital (teaching vs not). Results: Of 85,050 patients with AP (median age 53 (range 18-90), 49% female), 1218 had CDI (1.43%). Patients with AP and CDI had increased odds of inpatient mortality (adjusted odds ratio, 1.9; 95% CI (1.5-2.5)), a longer LOS (14.2 vs 5.6 d; p < 0.0001), and greater hospital charges ($126,818 vs $46,041; p < 0.001) compared with AP patients without CDI. Patients with CDI and AP had an increased odds of mechanical ventilation (adjusted odds ratio, 4.1; CI 95% (3.5-4.8)), acute renal failure (adjusted odds ratio, 2.4; 95 % CI (2.1-2.8)) and acute respiratory failure (adjusted odds ratio, 3.4; CI 95% (3.0-3.9)). Conclusion: In patients with AP, CDI is an uncommon complication but is associated with greater mortality, LOS, total charges, acute renal failure and acute respiratory failure.

Antibiotic exposure can lead to unintended outcomes, including drug-drug interactions, adverse drug events, and healthcare-associated infections like Clostridioides difficile infection (CDI). Improving antibiotic use is critical to reduce an individual’s CDI risk. Antibiotic stewardship initiatives can reduce inappropriate antibiotic prescribing (e.g., unnecessary antibiotic prescribing, inappropriate antibiotic selection), impacting both hospital (healthcare)-onset (HO)-CDI and community-associated (CA)-CDI. Previous computational and mathematical modeling studies have demonstrated a reduction in CDI incidence associated with antibiotic stewardship initiatives in hospital settings. Although the impact of antibiotic stewardship initiatives in long-term care facilities (LTCFs), including nursing homes, and in outpatient settings have been documented, the effects of specific interventions on CDI incidence are not well understood. We examined the relative effectiveness of antibiotic stewardship interventions on CDI incidence using a geospatially explicit agent-based model of a regional healthcare network in North Carolina. We simulated reductions in unnecessary antibiotic prescribing and inappropriate antibiotic selection with intervention scenarios at individual and network healthcare facilities, including short-term acute care hospitals (STACHs), nursing homes, and outpatient locations. Modeled antibiotic prescription rates were calculated using patient-level data on antibiotic length of therapy for the 10 modeled network STACHs. By simulating a 30% reduction in antibiotics prescribed across all inpatient and outpatient locations, we found the greatest reductions on network CDI incidence among tested scenarios, namely a 17% decrease in HO-CDI incidence and 7% decrease in CA-CDI. Among intervention scenarios of reducing inappropriate antibiotic selection, we found a greater impact on network CDI incidence when modeling this reduction in nursing homes alone compared to the same intervention in STACHs alone. These results support the potential importance of LTCF and outpatient antibiotic stewardship efforts on network CDI burden and add to the evidence that a coordinated approach to antibiotic stewardship across multiple facilities, including inpatient and outpatient settings, within a regional healthcare network could be an effective strategy to reduce network CDI burden.

Adherence to Clostridium difficile Infection Treatment Guidelines at a Tertiary Care Hospital: A Retrospective Chart Review

PIN25 - Cost-Effectiveness Analysis of Fecal Microbiota Transplantation in Patients With Clostridium Difficile Infection in Hong Kong

Background and ObjectiveOmadacycline is an aminomethylcycline antibiotic approved in the USA as once-daily intravenous/oral monotherapy for adults with community-acquired bacterial pneumonia (CABP). Omadacycline demonstrated noninferiority to the fluoroquinolone moxifloxacin in a phase III CABP trial; adverse-event rates were similar between treatment groups except for Clostridioides difficile infection (CDI), which occurred in 2% of moxifloxacin-treated patients and 0% of patients on omadacycline. Conceptual healthcare-decision analytic models were developed to better understand the economic implications of antibiotic selection and CDI risk in acute-care facilities.MethodsA conceptual healthcare-decision analytic model was created to estimate incremental costs associated with treating 100 hospitalized CABP patients with an initial 5-day inpatient regimen of omadacycline instead of moxifloxacin. The underlying model assumption was that treatment with omadacycline has the potential to reduce CDI events relative to moxifloxacin. The model included excess costs associated with each treatment group from admission through discharge. Attributable CDI cost per case in the moxifloxacin group varied from $15,000 to $45,000 (US$). Omadacycline acquisition cost was $300–600/day for 5 days.ResultsAt a CDI attributable cost per case of $30,000 (base-case analyses), the incremental treatment cost (US$) per 100 patients ranged from $300,000 to $− 120,000 (cost savings). The excess CDI incidence in moxifloxacin-treated patients would need to be 5–10% for omadacycline to be cost-saving, assuming the attributable CDI cost is approximately $30,000.ConclusionTargeted omadacycline use may reduce economic burden associated with hospitalized CABP patients treated with moxifloxacin if it can reduce excess cases of moxifloxacin-associated CDI.

IntroductionClostridium difficile infection (CDI) is the major cause of infectious nosocomial diarrhoea and is associated with considerable morbidity, mortality and economic impact. Bezlotoxumab administered in combination with standard of care (SoC) antibiotic therapy prevents recurrent CDI. This study assessed the cost-effectiveness of bezlotoxumab added to SoC, compared to SoC alone, to prevent the recurrence of CDI in high-risk patients from the Spanish National Health System perspective.MethodsA Markov model was used to simulate the natural history of CDI over a lifetime horizon in five populations of patients at high risk of CDI recurrence according to MODIFY trials: (1) ≥ 65 years old; (2) severe CDI; (3) immunocompromised; (4) ≥ 1 CDI episode in the previous 6 months; and (5) ≥ 65 years old and with ≥ 1 CDI episode in the previous 6 months. The incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.ResultsIn all patient populations (from 1 to 5), bezlotoxumab added to SoC reduced CDI recurrence compared to SoC alone by 26.4, 19.5, 21.2, 26.6 and 39.7%, respectively. The resulting ICERs for the respective subgroups were €12,724, €17,495, €9545, €7386, and €4378. The model parameters with highest impact on the ICER were recurrence rate (first), mortality, and utility values. The probability that bezlotoxumab was cost-effective at a willingness-to-pay threshold of €21,000/QALY was 85.5%, 54.1%, 86.0%, 94.5%, 99.6%, respectively.ConclusionThe results suggest that bezlotoxumab added to SoC compared to SoC alone is a cost-effective treatment to prevent the recurrence of CDI in high-risk patients. The influence of changes in model parameters on DSA results was higher in patients ≥ 65 years old, with severe CDI and immunocompromised. Additionally, PSA estimated that the probability of cost-effectiveness exceeded 85% in most subgroups.FundingMerck Sharp & Dohme Corp.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0813-y) contains supplementary material, which is available to authorized users.

PIN35 - COST-EFFECTIVENESS OF BEZLOTOXUMAB FOR THE PREVENTION OF RECURRENCE OF CLOSTRIDIUM DIFFICILE INFECTION IN PORTUGAL

BackgroundProton pump inhibitors (PPIs) are a known risk factor for Clostridioides difficile infection (CDI) and recurrence, even in the absence of antibiotic use. No studies have specifically assessed the increased risk for CDI based on PPI duration, given that PPIs are frequently newly prescribed during hospitalizations and infrequently discontinued, even when CDI has occurred. The aim of this project was to assess the time course of PPI utilization and risk of CDI.MethodsWe conducted a retrospective matched case–control study comparing patients who developed CDI (cases) with patients who did not develop CDI (controls, matched on age, gender, date of admission and hospital location) from a cohort of patients with a C.difficile PCR test order from an academic medical center. Patient charts were reviewed for PPI use prior to the date of the positive test and whether the PPI was started in the hospital or as a home medication (>30d, 30–90d, 90–180d, >180d). The primary comparison was odds of PPI use between cases and controls using conditional logistic regression adjusted for antibiotic exposure (SAS 9.4, Cary, NC).ResultsA total of 348 patients were included in the study, 174 cases and 174 matched controls. 65% of patients in the study received a PPI, 85% a PPI or H2 blocker and 95% of patients received antibiotics during their admission. Patients on PPIs as home medications were not at an increased risk of CDI (OR = 1.08 (95% CI 0.60–1.93)) compared with those not on PPIs. Patients whose PPIs were initiated in the hospital were at increased risk of CDI compared with those not on PPIs (OR = 1.4 (95% CI 0.81–2.41)). No significant difference was observed across time periods of PPI use prior to admission and development of CDI.ConclusionPatients who started PPIs during inpatient stays were at a higher risk of developing CDI than patients not exposed to PPIs. However, PPI use was not found to be significantly associated with CDI in this analysis, regardless of the time or duration of PPI prescription. The results may be confounded by the high frequency of PPI use and concomitant antibiotic use in both cases and controls. Further study is needed to evaluate the impact of short-course PPI prescriptions in inpatient settings on CDI.DisclosuresAll authors: No reported disclosures.

Service Use and Cost in 2002 Among Clients in Community Settings Who Were Discharged From a State Hospital in 1989

BACKGROUND. Underlying stroke is often misdiagnosed in patients presenting with dizziness. Although such patients are usually ineligible for acute stroke treatment, accurate diagnosis may still improve outcomes through selection of patients for secondary prevention measures. OBJECTIVE. The purpose of our study was to investigate the cost-effectiveness of differing neuroimaging approaches in the evaluation of patients presenting to the emergency department (ED) with dizziness who are not candidates for acute intervention. METHODS. A Markov decision-analytic model was constructed from a health care system perspective for the evaluation of a patient presenting to the ED with dizziness. Four diagnostic strategies were compared: noncontrast head CT, head and neck CTA, conventional brain MRI, and specialized brain MRI (including multiplanar high-resolution DWI). Differing long-term costs and outcomes related to stroke detection and secondary prevention measures were compared. Cost-effectiveness was calculated in terms of lifetime expenditures in 2022 U.S. dollars for each quality-adjusted life year (QALY); deterministic and probabilistic sensitivity analyses were performed. RESULTS. Specialized MRI resulted in the highest QALYs and was the most cost-effective strategy with US$13,477 greater cost and 0.48 greater QALYs compared with noncontrast head CT. Conventional MRI had the next-highest health benefit, although was dominated by extension with incremental cost of US$6757 and 0.25 QALY; CTA was also dominated by extension, with incremental cost of US$3952 for 0.13 QALY. Non-contrast CT alone had the lowest utility among the four imaging choices. In the deterministic sensitivity analyses, specialized MRI remained the most cost-effective strategy. Conventional MRI was more cost-effective than CTA across a wide range of model parameters, with incremental cost-effectiveness remaining less than US$30,000/QALY. Probabilistic sensitivity analysis yielded similar results as found in the base-case analysis, with specialized MRI being more cost-effective than conventional MRI, which in turn was more cost-effective than CTA. CONCLUSION. The use of MRI in patients presenting to the ED with dizziness improves stroke detection and selection for subsequent preventive measures. MRI-based evaluation leads to lower long-term costs and higher cumulative QALYs. CLINICAL IMPACT. MRI, incorporating specialized protocols when available, is the preferred approach for evaluation of patients presenting to the ED with dizziness, to establish a stroke diagnosis and to select patients for secondary prevention measures.

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

To compare the cost-effectiveness of budesonide-formoterol in a single inhaler used as both maintenance and reliever medication versus clinician-directed titration of salmeterol-fluticasone as maintenance medication, plus salbutamol taken as needed, in controlling asthma in adults and adolescents. A Canadian economic evaluation was conducted based on the results of a large (n=2143), open-label, randomized, controlled effectiveness trial in which health resource use was prospectively collected. The primary outcome measurement was the time to the first severe exacerbation. Costs included direct medical costs (physician and emergency room visits, hospitalizations, asthma drug costs, etc) and productivity (absenteeism). The time horizon was one year, which corresponded to the duration of the clinical trial. Prices were obtained from 2005 Canadian sources. Both health care and societal perspectives were considered, and deterministic univariate sensitivity analyses were conducted. In the clinical trial, budesonide-formoterol as maintenance and reliever treatment was superior to salmeterol-fluticasone with respect to the time to the first severe exacerbation, overall rate of exacerbations and use of as-needed reliever medication. The annualized rate of severe exacerbations was 0.24 events/patient in the budesonide-formoterol arm and 0.31 events/patient in the salmeterol-fluticasone arm (P=0.0025). From a health care perspective, the mean cost per patient-year was $1,315 in the budesonide-formoterol arm versus $1,541 in the salmeterol-fluticasone arm. From a societal perspective, the mean cost per patient-year was $1,538 in the budesonide-formoterol arm and $1,854 in the salmeterol-fluticasone arm. Budesonide-formoterol was dominant (more effective and less expensive) in the base case analysis from both perspectives. The results were robust under sensitivity testing. The strategy that allows budesonide-formoterol to be used in a single inhaler as both maintenance and reliever medication proved to be more effective and less expensive than a strategy of clinician-directed titration of salmeterol-fluticasone with salbutamol as reliever therapy.